Process for the synthesis of 2,5-dihydroxyterephtalic acid

ABSTRACT

2,5-dihydroxyterephthalic acid is produced in high yields and high purity from 2,5-dihaloterephthalic acid by contact with a copper source and a ligand that coordinates to copper under basic conditions.

TECHNICAL FIELD

This invention relates to the manufacture of hydroxybenzoic acids, whichare valuable for a variety of purposes such as use as intermediates oras monomers to make polymers.

BACKGROUND

Hydroxybenzoic acids are useful as intermediates in the manufacture ofmany valuable materials including pharmaceuticals and compounds activein crop protection, and are also useful as monomers in the production ofpolymers. In particular, 2,5-dihydroxyterephthalic acid (Formula I,“DHTA”) is a useful monomer for the synthesis of high strength fiberssuch as those made frompoly[(1,4-dihydrodiimidazo[4,5-b:4′,5′-e]pyridine-2,6-diyl)(2,5-dihydroxy-1,4-phenylene)].

Various preparations of 2,5-dihydroxyterephthalic acid and otherhydroxybenzoic acids are known. Marzin, in Journal fuer PraktischeChemie, 1933, 138, 103-106, teaches the synthesis of2,5-dihydroxyterephthalic acid from 2,5-dibromoterephthalic acid(Formula II, “DBTA”) in the presence of copper powder.

Singh et al, in Jour. Indian Chem. Soc., Vol. 34, No. 4, pages 321˜323(1957), report the preparation of a product that includes DHTA by thecondensation of DBTA with phenol in the presence of KOH and copperpowder.

Rusonik et al, Dalton Transactions, 2003, 2024-2028, describe thetransformation of 2-bromobenzoic acid into salicylic acid, benzoic acid,and diphenoic acid in a reaction catalyzed by Cu(I) in the presence ofvarious ligands. A tertiary tetraamine minimizes the formation ofdiphenoic acid in use with Cu(I).

Comdom et al, Synthetic Communications, 32(13), 2055-59 (2002), describea process for the synthesis of salicylic acids from 2-chlorobenzoicacids. Stoichiometric amounts of pyridine (0.5 to 2.0 moles per mole of2-chlorobenzoic acid) are used such as at least 1.0 mole pyridine permole 2-chlorobenzoic acid. Cu powder is used as a catalyst along withthe pyridine.

The various prior art processes for making hydroxybenzoic acids arecharacterized by long reaction times, limited conversion resulting insignificant productivity loss, or the need to run under pressure and/orat higher temperatures (typically 140 to 250° C.) to get reasonablerates and productivity. A need therefore remains for a process by which2,5-dihydroxy terephthalic acid can be produced economically; with lowinherent operational difficulty; and with high yields and highproductivity in both small- and large-scale operation, and in batch andcontinuous operation.

SUMMARY

One embodiment of this invention provides a process for preparing2,5-dihydroxyterephthalic acid by (a) contacting a2,5-dihaloterephthalic acid (III)

where X=Cl, Br, or Iwith base in water to form therefrom the corresponding dibasic salt of2,5-dihaloterephthalic acid; (b) contacting the dibasic salt of2,5-dihaloterephthalic acid with base in water, and with a copper sourcein the presence of a ligand that coordinates to copper, to form thedibasic salt of 2,5-dihydroxyterephthalic acid from the dibasic salt of2,5-dihaloterephthalic acid at a solution pH of at least about 8; (c)optionally, separating the dibasic salt of 2,5-dihydroxyterephthalicacid from the reaction mixture in which it is formed; and (d) contactingthe dibasic salt of 2,5-dihydroxyterephthalic acid with acid to formtherefrom 2,5-dihydroxyterephthalic acid.

In another embodiment, the ligand may be an amine ligand, and in afurther embodiment the ligand includes, when it is a tetraamine ligand,at least one primary or secondary amino group.

Yet another embodiment of this invention provides a process forpreparing a 2,5-dialkoxyterephthalic acid by preparing a2,5-dihydroxyterephthalic acid in the manner described above and thenconverting the 2,5-dihydroxyterephthalic acid to a2,5-dialkoxyterephthalic acid.

Yet another embodiment of this invention consequently provides a processfor preparing 2,5-dialkoxyterephthalic acid by (a) contacting a2,5-dihaloterephthalic acid (III)

where X=Cl, Br, or Iwith base in water to form therefrom the corresponding dibasic salt of2,5-dihaloterephthalic acid; (b) contacting the dibasic salt of2,5-dihaloterephthalic acid with base in water, and with a copper sourcein the presence of a ligand that coordinates to copper, to form thedibasic salt of 2,5-dihydroxyterephthalic acid from the dibasic salt of2,5-dihaloterephthalic acid at a solution pH of at least about 8; (c)optionally, separating the dibasic salt of 2,5-dihydroxyterephthalicacid from the reaction mixture in which it is formed; (d) contacting thedibasic salt of 2,5-dihydroxyterephthalic acid with acid to formtherefrom a 2,5-dihydroxyterephthalic acid; and (e) converting the2,5-dihydroxyterephthalic acid to a 2,5-dialkoxyterephthalic acid.

Yet another embodiment of this invention provides a process forpreparing a 2,5-dihydroxyterephthalic acid or a 2,5-dialkoxyterephthalicacid as described above that further includes a step of subjecting the2,5-dihydroxyterephthalic acid or the 2,5-dialkoxyterephthalic acid to areaction to prepare therefrom a compound, monomer, oligomer or polymer.

Yet another embodiment of this invention consequently provides a processfor preparing a compound, monomer, oligomer or polymer by (a) contactinga 2,5-dihaloterephthalic acid (III)

where X =Cl, Br, or Iwith base in water to form therefrom the corresponding dibasic salt of2,5-dihaloterephthalic acid; (b) contacting the dibasic salt of2,5-dihaloterephthalic acid with base in water, and with a copper sourcein the presence of a ligand that coordinates to copper, to form thedibasic salt of 2,5-dihydroxyterephthalic acid from the dibasic salt of2,5-dihaloterephthalic acid at a solution pH of at least about 8; (c)optionally, separating the dibasic salt of 2,5-dihydroxyterephthalicacid from the reaction mixture in which it is formed; (d) contacting thedibasic salt of 2,5-dihydroxyterephthalic acid with acid to formtherefrom 2,5-dihydroxyterephthalic acid; (e) optionally, converting the2,5-dihydroxyterephthalic acid to a 2,5-dialkoxyterephthalic acid; and(f) subjecting the 2,5-dihydroxyterephthalic acid and/or the2,5-dialkoxyterephthalic acid to a reaction to prepare therefrom acompound, monomer, oligomer or polymer.

DETAILED DESCRIPTION

This invention provides a high yield and high productivity process forpreparing a 2,5-dihydroxyterephthalic acid by contacting a2,5-dihaloterephthalic acid with base to form the dibasic salt of2,5-dihaloterephthalic acid; contacting the dibasic salt of2,5-dihaloterephthalic acid with base, and with a copper source in thepresence of an amine ligand that coordinates to copper, to form thedibasic salt of 2,5-dihydroxyterephthalic acid; and then contacting thedibasic salt of 2,5-dihydroxyterephthalic acid with acid to form the2,5-dihydroxyterephthalic acid product. The term “dibasic salt” as usedherein denotes the salt of a dibasic acid, which is an acid thatcontains two replaceable hydrogen atoms per molecule.

Suitable dihaloterephthalic acids with which the process of thisinvention is started include 2,5-dibromoterephthalic acid,2,5-dichloroterephthalic acid, and 2,5-diiodoterephthalic acid, ormixtures thereof. 2,5-dibromoterephthalic acid (“DBTA”)is commerciallyavailable. It can, however, be synthesized, for example, by oxidation ofp-xylene in aqueous hydrogen bromide (McIntyre et al, Journal of theChemical Society, Abstracts, 1961, 4082-5), by bromination ofterephthalic acid or terephthaloyl chloride (U.S. Pat. No. 3,894,079),or by oxidation of 2,5-dibromo-1,4-dimethylbenzene (DE 1,812,703).2,5-dichloroterephthalic acid is also commercially available. It can,however, be synthesized, for example, by oxidation of2,5-dichloro-1,4-dimethylbenzene [Shcherbina et al, Zhurnal PrikladnoiKhimii (Sankt-Peterburg, Russian Federation, 1990)], 63(2), 467-70.2,5-diiodoterephthalic acid can be synthesized, for example, byoxidation of 2,5-diiodo-1,4-dimethylbenzene [Perry et al, Macromolecules(1995), 28(10), 3509-15].

In step (a), 2,5-dihaloterephthalic acid is contacted with base in waterto form therefrom the corresponding dibasic salt of2,5-dihaloterephthalic acid. In step (b), the dibasic salt of2,5-dihaloterephthalic acid is contacted with base in water, and with acopper source in the presence of a ligand that coordinates to copper, toform the dibasic salt of 2,5-dihydroxyterephthalic acid from the dibasicsalt of 2,5-dihaloterephthalic acid.

The base used in step (a) and/or step (b) may be an ionic base, and mayin particular be one or more of a hydroxide, carbonate, bicarbonate,phosphate or hydrogen phosphate of one or more of Li, Na, K, Mg or Ca.The base used may be water-soluble, partially water-soluble, or thesolubility of the base may increase as the reaction progresses and/or asthe base is consumed. NaOH and Na₂CO₃ are preferred, but other suitableorganic bases may be selected, for example, from the group consisting oftrialkylamines (such as tributylamine);N,N,N′,N′-tetramethylethylenediamine; and N-alkyl imidazoles (forexample, N-methylimidazole). In principle any base capable ofmaintaining a pH above 8 and/or binding the acid produced during thereaction of the 2,5-dihaloterephthalic acid is suitable.

The specific amounts of base to be used in steps (a) and/or (b) dependon the strength of the base. In step (a), 2,5-dihaloterephthalic acid ispreferably contacted with at least about two equivalents of base,preferably a water-soluble base, per equivalent of2,5-dihaloterephthalic acid. One “equivalent” as used for a base in thiscontext is the number of moles of base that will react with one mole ofhydrogen ions; for an acid, one equivalent is the number of moles ofacid that will supply one mole of hydrogen ions.

In step (b), enough base should be used to maintain a solution pH of atleast about 8, or at least about 9, or at least about 10, and preferablybetween about 9 and about 11. Thus, typically in step (b), the dibasicsalt of 2,5-dihaloterephthalic acid is contacted with at least about twoequivalents of base, such as a water-soluble base, per equivalent of thedibasic salt of 2,5-dihaloterephthalic acid.

In alternative embodiments, however, it may be desirable in steps (a)and (b) to use a total of at least about 4 to about 5 equivalents ofbase, such as a water-soluble base, in the reaction mixture perequivalent of 2,5-dihaloterephthalic acid originally used at the startof the reaction. A base used in an amount as described above istypically a strong base, and is typically added at ambient temperature.The base used in step (b) may be the same as, or different than, thebase used in step (a).

As mentioned above, in step (b), the dibasic salt of2,5-dihaloterephthalic acid is also contacted with a copper source inthe presence of a ligand that coordinates to copper. The copper sourceand the ligand may be added sequentially to the reaction mixture, or maybe combined separately (for example, in a solution of water oracetonitrile) and added together. The copper source may be combined withthe ligand in the presence of oxygen in water, or be combined with asolvent mixture containing water.

From the presence together in the reaction mixture of the copper sourceand the ligand, in a basic solution of the dibasic salt of the2,5-dihaloterephthalic acid, there is obtained an aqueous mixturecontaining the dibasic salt of 2,5-dihydroxyterephthalic acid, copperspecie(s), the ligand, and a halide salt. If desired, the dibasic saltof 2,5-dihydroxyterephthalic acid may, at this stage and before theacidification in step (d), be separated from the mixture [as optionalstep (c)], and may be used as a dibasic salt in another reaction or forother purposes.

The dibasic salt of 2,5-dihydroxyterephthalic acid is then contacted instep (d) with acid to convert it to the 2,5-dihydroxyterephthalic acidproduct. Any acid of sufficient strength to protonate the dibasic saltis suitable. Examples include without limitation hydrochloric acid,sulfuric acid and phosphoric acid.

The reaction temperature for steps (a) and (b) is preferably betweenabout 40 and about 120° C., more preferably between about 75 and about95° C.; and the process thus in various embodiments involves a step ofheating the reaction mixture. The solution is typically allowed to coolbefore the acidification in step (d) is carried out. In variousembodiments, oxygen may be excluded during the reaction.

The copper source is copper metal [“Cu(0)”], one or more coppercompounds, or a mixture of copper metal and one or more coppercompounds. The copper compound may be a Cu(I) salt, a Cu(II) salt, ormixtures thereof. Examples include without limitation CuCl, CuBr, CuI,Cu₂SO₄, CuNO₃, CuCl₂, CuBr₂, CuI₂, CuSO₄, and Cu(NO₃)₂. CuBr ispreferred. The amount of copper provided is typically about 0.1 to about5 mol % based on moles of 2,5-dihaloterephthalic acid.

When the copper source is Cu(0), Cu(0), copper bromide and a ligand maybe combined in the presence of air. In the case of Cu(0) or Cu(I), apredetermined amount of metal and ligand may be combined in water, andthe resulting mixture may be reacted with air or dilute oxygen until acolored solution is formed. The resulting metal/ligand solution is addedto the reaction mixture containing the dibasic salt of2,5-dihaloterephthalic acid and base in water.

The ligand may be a straight- or branched-chain or cyclic, aliphatic oraromatic, substituted or unsubstituted, amine, or a mixture of two ofmore such ligands. Whether formed as a compound, an oligomer or polymer,conventional nomenclature may be used to describe the number of aminegroups present in the ligand, such as a mono-, di-, tri-, tetra-,penta-, hexa-, hepta- or octaamine, and so on. In its unsubstitutedform, the ligand may be an organoamine that contains carbon, nitrogenand hydrogen atoms only. In it substituted form, the amine ligand maycontain hetero atoms such as oxygen or sulfur. In various embodiments,particularly but not exclusively as relates to the tetraamines, theamine may contain at least one primary or secondary amino group.

Primary or secondary monoamines suitable for use herein as the ligandinclude those described generally by the following Formula 11

wherein R¹ and R² are each independently selected from H;

a C₁˜C₁₀ straight-chain or branched, saturated or unsaturated,substituted or unsubstituted, hydrocarbyl radical;

a C₃˜C₁₂ cyclic aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl radical; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl radical.

In certain embodiments, R¹ and/or R² may for example be a methyl, ethyl,propyl, butyl, pentyl, hexyl or phenyl radical. In other embodiments, atleast one of R¹ and R² is not H. Particular monoamines suitable for useherein as the ligand include ethyl amine, isopropylamine, sec-butylamine, dimethyl amine, methyl ethyl amine, ethyl-n-butyl amine,allylamine, cyclohexyl amine, N-ethylcyclohexyl amine, aniline, N-ethylaniline, toluidine and xylidine.

Primary or secondary diamines suitable for use herein as the ligandinclude those described generally by the following Formula 12

wherein each R¹ and each R² is independently H;

a C₁˜C₁₀ straight-chain or branched, saturated or unsaturated,substituted or unsubstituted, hydrocarbyl radical;

a C₃˜C₁₂ cyclic aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl radical; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl radical; or

wherein R³ and R⁴ are each independently H;

a C₁˜C₁₀ straight-chain or branched, saturated or unsaturated,substituted or unsubstituted, hydrocarbyl radical;

a C₃˜C₁₂ cyclic aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl radical; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl radical; or

R³ and R⁴ are joined to form a ring structure that is

a C₄˜C₁₂ aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl ring structure; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl ringstructure; and

wherein a, b, and c are each independently 0˜4.

In certain embodiments, one or both of the R¹s is H. In otherembodiments, one or both of the R²s is also H. In other embodiments, anyone or more of R¹ to R⁴ may be a methyl, ethyl, propyl, butyl, pentyl,hexyl or phenyl radical.

In various particular embodiments, a, b and c may all equal 0, andeither R³=R⁴=H, or R³ and R⁴ are joined to form an aliphatic ringstructure. Particularly when b=0, the aliphatic ring structure may be acyclohexylene group, which is the divalent radical, —C₆H₁₀—, as shownbelow, thus providing a cyclohexyl diamine:

The formation of a cyclohexylene group from R³ and R⁴ may be illustratedgenerally by the following structure:

where R¹, R², a and c are as set forth above. In alternativeembodiments, however, one amino group, or the alkyl radical on which itis located, may be in the meta or para position on the cycloalkyl oraromatic ring to the other amino group.

Suitable aliphatic diamines may include N,N′-di-n-alkylethylene diaminesand N,N′-di-n-alkylcyclohexane-1,2-diamines. Specific examples includewithout limitation N,N′-dimethylethylene diamine, N,N′-diethylethylenediamine, N,N′-di-n-propylethylene diamine, N,N′-dibutylethylene diamine,N,N′-dimethylcyclohexane-1,2-diamine,N,N′-diethylcyclohexane-1,2-diamine,N,N′-di-n-propylcyclohexane-1,2-diamine, andN,N′-dibutylcyclohexane-1,2-diamine. Examples of suitable aromaticdiamines include without limitation 1,2-phenylenediamine andN,N′-dialkylphenylene diamines such asN,N′-dimethyl-1,2-phenylenediamine andN,N′-diethyl-1,2-phenylenediamine; and benzidine.

Primary or secondary tri- and higher amines suitable for use herein asthe ligand may be described generally by the following Formula 13:

wherein each R¹, R², R³, R⁴, R⁵ and R⁶ is independently selected from;

H;

a C₁˜C₁₀ straight-chain or branched, saturated or unsaturated,substituted or unsubstituted, hydrocarbyl radical;

a C₃˜C₁₂ cyclic aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl radical; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl radical; and

wherein a is 2˜4, b and c is each independently 0˜4; and m≧0.

In certain embodiments, one or both of the R¹s, or at least one R³, orat least one R⁴, or R⁵, and/or R⁶ is H. In other particular embodiments,m=0, 1, 2, 3, 4 or 5. In yet other embodiments, R³=R⁴=R⁶=H; and/or oneor both of R¹ and R²=H. In further embodiments, any one or more of R¹through R⁵ may be a methyl, ethyl, propyl, butyl, pentyl, hexyl orphenyl radical.

Amines according to Formula 13 suitable for use herein as the ligandinclude, for example, those described generally by the following Formula14:

wherein x is 2˜10. Formula 14 describes various polyethyleneamineswhere, in Formula 13, each R group is H, a=2, b=c=0, and m=0 to 8.

Other amines according to Formula 13, or other higher amines, suitablefor use herein as the ligand include diethylenetriamine andtriethylenetetramine, as well as those described generally by thefollowing structures:

The ligand may also be a cyclic amine compound that is a molecule havingat least one closed ring structure in which at least one ring atom isnitrogen. This form of ligand is then heterocyclic in the sense that thering structure will contain, in addition to nitrogen atoms, other atomsthat are primarily carbon and hydrogen, but may also be oxygen and/orsulfur, as described below. The nitrogen atom may for example be amember of

a C₄˜C₁₂ aliphatic, saturated or unsaturated, substituted orunsubstituted hydrocarbyl ring structure; or

a C₅˜C₁₂ aromatic, substituted or unsubstituted hydrocarbyl ringstructure.

Examples of various nitrogen-containing, cyclic compounds suitable foruse herein as the ligand include without limitation quinolione, indole,imidazole, ethylenimine, as well as those described by the followingstructures:

The “hydrocarbyl” groups referred to above in the descriptions ofligands suitable for use herein are, when unsubstituted, univalentgroups containing only carbon and hydrogen. Similarly, an unsubstitutedamine is a compound that contains in its structure nitrogen, carbon andhydrogen atoms only. In any of the hydrocarbyl radicals or ringstructures described above, however, one or more O or S atoms mayoptionally be substituted for any one or more of the in-chain or in-ringcarbon atoms, provided that the resulting structure contains no —O—O— or—S—S— moieties, and provided that no carbon atom is bonded to more thanone heteroatom. An example of a suitable ligand in which an oxygen atomhas been substituted for a carbon atom is shown in Formula 15:

wherein q may have, for example, an average value of about 3 in amixture of molecules with different molecular weights.

Other examples of ligands suitable for use herein and having oxygensubstitution include anisidine, phenetidine, as well as those describedgenerally by the following structures:

Ligands of particular versatility include secondary amines, particularlyN,N′-substituted 1,2-diamines, including those that that may bedescribed as R⁷NH—(CHR⁸CHR⁹)—NHR¹⁰ wherein R⁷ and R¹⁰ are eachindependently chosen from the group of C₁-C₄ primary alkyl radicals, andR⁸ and R⁹ are each independently chosen from the group of H and C₁-C₄alkyl radicals, and/or where R⁸ and R⁹ may be joined to form a ringstructure.

When, in Formula 12, R³ and R⁴ are joined to form an aromatic ringstructure, and/or when a cyclic amine ligand contains one or morearomatic ring structures, more severe reaction conditions (e.g. highertemperature, or larger amounts of copper and/or ligand) may be needed toachieve high conversion, selectivity, yield and/or purity in thereaction.

A ligand suitable for use herein may be selected as any one or more orall of the members of the whole population of ligands described by nameor structure above. A suitable ligand may, however, also be selected asany one or more or all of the members of a subgroup of the wholepopulation, where the subgroup may be any size (1, 2, 6, 10 or 20, forexample), and where the subgroup is formed by omitting any one or moreof the members of the whole population as described above. As a result,the ligand may in such instance not only be selected as one or more orall of the members of any subgroup of any size that may be formed fromthe whole population of ligands as described above, but the ligand mayalso be selected in the absence of the members that have been omittedfrom the whole population to form the subgroup. For example, in certainembodiments, the ligand useful herein may be selected as one or more orall of the members of a subgroup of ligands that excludes from the wholepopulation pyridine, 2,5,8,11-tetramethyl-2,5,8,11-tetraazadodecane,and/or 1,1,4,7,10,10-hexamethyltriethylenetetraamine, with or withoutthe exclusion from the whole population of other ligands too.

In various embodiments, the ligand may be provided in an amount of about1 to about 8, preferably about 1 to about 2, molar equivalents of ligandper mole of copper. In those and other embodiments, the ratio of molarequivalents of ligand to molar equivalents of dihaloterephthalic acidmay be less than or equal to about 0.1. As used herein, the term “molarequivalent” indicates the number of moles of ligand that will interactwith one mole of copper.

In one embodiment, a Cu(I) salt may be selected as CuBr; the ligand isselected from the group consisting of N,N′-dimethylethylene diamine,N,N′-diethylethylene diamine, N,N′-di-n-propylethylene diamine,N,N′-dibutylethylene diamine, N,N′-dimethylcyclohexane-1,2-diamine,N,N′-diethylcyclohexane-1,2-diamine,N,N′-di-n-propylcyclohexane-1,2-diamine,N,N′-dibutylcyclohexane-1,2-diamine; and CuBr is combined with two molarequivalents of the ligand in the presence of water and air.

The ligand is believed to facilitate the action of the copper source asa catalyst, and/or the copper source and the ligand are believed tofunction together to act as a catalyst, to improve one or moreattributes of the reaction.

The process described above also allows for effective and efficientsynthesis of related compounds, such as a 2,5-dialkoxy terephthalicacid, which may be described generally by the structure of Formula VI:

wherein R⁹ and R¹⁰ are each independently a substituted or unsubstitutedC₁₋₁₀ alkyl group. R⁹ and R¹⁰ are, when unsubstituted, univalent groupscontaining only carbon and hydrogen. In any of those alkyl groups,however, one or more O or S atoms may optionally be substituted for anyone or more of the in-chain carbon atoms, provided that the resultingstructure contains no —O—O— or —S—S— moieties, and provided that nocarbon atom is bonded to more than one heteroatom.

A 2,5-dihydroxy terephthalic acid, as prepared by the process of thisinvention, may be converted to a 2,5-dialkoxy terephthalic acid, andsuch conversion may be accomplished, for example, by contacting a2,5-dihydroxy terephthalic acid under basic conditions with a dialkylsulfate of the formula R⁹ R¹⁰ SO₄. One suitable method of running such aconversion reaction is as described in Austrian Patent No. 265,244.Suitable basic conditions for such conversion are a solution pH of atleast about 8, or at least about 9, or at least about 10, and preferablyabout 9 to about 11, using one or more bases such as described above.

In certain embodiments, it may be desired to separate the2,5-dihydroxyterephthalic acid from the reaction mixture in which it wasformed before converting it to a 2,5-dialkoxyterephthalic acid.

The process described above also allows for effective and efficientsynthesis of products made from the resulting 2,5-dihydroxyterephthalicacid or 2,5-dialkoxyterephthalic acid such as a compound, a monomer, oran oligomer or polymer thereof. These produced materials may have one ormore of ester functionality, ether functionality, amide functionality,imide functionality, imidazole functionality, carbonate functionality,acrylate functionality, epoxide functionality, urethane functionality,acetal functionality, and anhydride functionality.

Representative reactions involving a material made by the process ofthis invention, or a derivative of such material, include, for example,making a polyester from a 2,5-dihydroxyterephthalic acid and eitherdiethylene glycol or triethylene glycol in the presence of 0.1% ofZN₃(BO₃)₂ in 1-methylnaphthalene under nitrogen, as disclosed in U.S.Pat. No. 3,047,536 (which is incorporated in its entirety as a parthereof for all purposes). Similarly, a 2,5-dihydroxyterephthalic acid isdisclosed as suitable for copolymeriztion with a dibasic acid and aglycol to prepare a heat-stabilized polyester in U.S. Pat. No. 3,227,680(which is incorporated in its entirety as a part hereof for allpurposes), wherein representative conditions involve forming aprepolymer in the presence of titanium tetraisopropoxide in butanol at200˜250° C., followed by solid-phase polymerization at 280° C. at apressure of 0.08 mm Hg.

A 2,5-dihydroxyterephthalic acid has also been polymerized with thetrihydrochloride-monohydrate of tetraaminopyridine in strongpolyphosphoric acid under slow heating above 100° C. up to about 180° C.under reduced pressure, followed by precipitation in water, as disclosedin U.S. Pat. No. 5,674,969 (which is incorporated in its entirety as apart hereof for all purposes); or by mixing the monomers at atemperature from about 50° C. to about 110° C., and then 145° C. to forman oligomer, and then reacting the oligomer at a temperature of about160° C. to about 250° C. as disclosed in U.S. Provisional ApplicationNo. 60/665,737, filed Mar. 28, 2005 (which is incorporated in itsentirety as a part hereof for all purposes), published as WO2006/104974. The polymer that may be so produced may be apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer such as apoly(l,4-(2,5-dihydroxy) phenylene-2,6-pyrido[2,3-d:5,6-d′]bisimidazole) polymer. The pyridobisimidazole portion thereofmay, however, be replaced by any or more of a benzobisimidazole,benzobisthiazole, benzobisoxazole, pyridobisthiazole and apyridobisoxazole; and the 2,5-dihydroxy-p-phenylene portion thereof maybe replace the derivative of one or more of isophthalic acid,terephthalic acid, 2,5-pyridine dicarboxylic acid, 2,6-naphthalenedicarboxylic acid, 4,4′-diphenyl dicarboxylic acid, 2,6-quinolinedicarboxylic acid, and 2,6-bis(4-carboxyphenyl)pyridobisimidazole.

EXAMPLES

This invention is further defined in the following examples. Theseexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, and do not limit the scope of theappended claims. From the above discussion and these examples, theessential characteristics of this invention may be ascertained, and,without departing from the spirit and scope thereof, modifications ofthe invention may be made to adapt it to various uses and conditions.

The following materials were used in the examples. All reagents wereused as received. Product purity was determined by ¹H NMR.

The ligands listed in Table 1 (labeled A through O, Q and R) wereobtained from Aldrich Chemical Company (Milwaukee, Wis.). Ligand P wasobtained from TCI America (Portland, Oreg.).

TABLE 1 Ligand Purity Code Ligand (%) A N,N-Dimethylethylenediamine 95 BN,N′-Diethylethylenediamine 95 C N,N′-Dimethyl-1,6-hexanediamine 98 DN,N-Diethyl-N′-methyethylenediamine 97 E 1,2-Phenylenediamine 98 Frac-trans-N,N′-Dimethylcyclohexane-1,2- 97 diamine GN-Methylethylenediamine 95 H 1,2-Bis(4-pyridyl)ethane 99 IN,N,N′,N′-tetramethylethylenediamine 99 J rac 1,2-Diaminocyclohexane 99K N,N′-Dimethylethylenediamine 99 L 1,10-Phenanthroline  99+ MEthylenediamine diacetate 98 N N,N′-Diisopropylethylene diamine 99 O1,1,4,7,10,10- 97 Hexamethyltriethylenetetramine P(1S,2S)-(+)-Dimethylcyclohexane-1,2- 95 diamine Q Pyridine >99  RBipyridyl >99 

2,5-dibromoterephthalic acid (95+% purity), except that used in Example1, was obtained from Maybridge Chemical Company Ltd.(Cornwall, UnitedKingdom ). The 2,5-dibromoterephthalic acid used in Example 1 wassynthesized according to the method described in DE 1,812,703.

Copper(I) bromide (“CuBr”) (98% purity) was obtained from Acros Organics(Geel, Belgium). Copper(II) bromide (“CuBr₂”) (99% purity), copper(II)chloride (“CuCl₂”) (97% purity), copper(I) triflate (“Cu(OTf)₂”) (97%purity), and copper (II)triflate(“Cu(OTf)”)(98% purity) were obtainedfrom Aldrich Chemical Company (Milwaukee, Wis., USA). Copper(II) sulfate(“CuSO₄”) (98% purity) was obtained from Strem Chemicals, Inc.(Newburyport, Mass., USA). Copper powder (99.5% purity), spherical,approximately 100 mesh, was obtained from Alfa Aesar (Ward Hill, Mass.).

Acetonitrile (99.8% purity) and Na₂CO₃ (99.5% purity) were obtained fromEM Science (Gibbstown, N.J.).

As used herein, the term “conversion” refers to how much reactant wasused up as a fraction or percentage of the theoretical amount. The term“selectivity” for a product P refers to the molar fraction or molarpercentage of P in the final product mix. The conversion multiplied bythe selectivity thus equals the maximum “yield” of P; the actual or“net” yield will normally be somewhat less than this because of samplelosses incurred in the course of activities such as isolating, handling,drying, and the like. The term “purity” denotes what percentage of thein-hand, isolated sample is actually the specified substance.

The terms “15% HCl” and “15% aqueous HCl” as used below denote aqueoushydrochloric acid whose concentration is 15 grams of HCl per 100 mL ofsolution. The terms “H₂O” and “water” refer to distilled water. Themeaning of abbreviations is as follows: “g” means gram(s), “mg” meansmilligram(s), “h” means hour(s), “kPa” means kilopascal, “M” meansmolar, “min” means minute(s), “mL” means milliliter(s), “mmol” meansmillimole(s), “NMR” means nuclear magnetic resonance spectroscopy, and“psi” means pounds per square inch.

Example 1

Under nitrogen, 5.00 g (15.4 mmol) of 2,5-dibromoterephthalic acid wascombined with 20 g of H₂O. 1.71 g (16.1 mmol) of Na₂CO₃ was then added.The mixture was heated to reflux with stirring for 30 min, remainingunder a nitrogen atmosphere. Another 2.38 g (22.5 mmol) of Na₂CO₃ wasadded to the reaction mixture and reflux was continued for 30 min.Separately, 28 mg of CuBr and 50 mg ofrac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F) were combinedwith 2 mL H₂O under nitrogen. The resulting mixture was stirred under anair atmosphere until the CuBr was dissolved to give a blue-purplesolution. This solution was added to the stirred reaction mixture at 90°C. under nitrogen and stirred for 2 h at 90° C. After cooling to 25° C.,the reaction mixture was acidified with 15% HCl, producing a yellowprecipitate. The yellow precipitate was filtered and washed with water.After drying, a total of 2.96 g (15 mmol, 97% yield)2,5-dihydroxyterphtalic acid was collected. The purity was determined by¹H NMR to be >98%.

Example 2

In a round bottom flask with reflux condenser, 1.00 g (3.1 mmol) of2,5-dibromoterephthalic acid was combined with 10 mL of H₂O. 0.85 g ofNa₂CO₃ (7.8 mmol) was added to this mixture. Subsequently, 0.12 mL(0.031 mmol, 1 mol %) of 0.23 M copper(I) bromide in acetonitrile wasadded, followed by addition of 0.12 mL (0.062 mmol, 2 mol %) of 0.5 Mrac-trans-N, N′-Dimethylcyclohexane-1,2-diamine (Ligand F). The reactionmixture was heated to 90° C. with stirring, then stirred for 18 h at 90°C. A sample was taken after 6 h and analyzed by ¹H NMR. No startingmaterial was detected. After 18 h, the conversion of2-bromo-5-hydroxyterephthalic acid was larger than 99%, and the productselectivity to 2,5-dihydroxyterephthalic acid was above 98%. Aftercooling to 25° C., the reaction mixture was acidified with 15% HCl,producing a light green precipitate. The precipitate was filtered andwashed with water and dried. The water phase did not show any detectableorganic products by ¹H NMR analysis. The purity of the solid product wasdetermined to >98%.

Examples 3˜19; Comparative Examples A and B

Under a nitrogen atmosphere, to a 2 mL vial with magnetic stir bar wasadded 25 mg (0.077 mmol) of 2,5-dibromoterephthalic acid (“DBTA”),followed by 0.308 mL (0.308 mmol) of 1.0 M aqueous sodium hydroxide and0.169 mL (0.169 mmol) of 1.0 M aqueous sodium acetate. The mixture wasthen treated with 0.003 mL (0.00077 mol, 1 mol %) of 0.23 M copper(I)bromide in acetonitrile and 0.003 mL (0.00154 mmol, 2 mol %) of thediamine ligand as noted below in Table 2, or half the amount fortetraamine ligand (Comparative Example A) or twice the amount in thecase of pyridine (Q). For Comparative Example B, no ligand was used.

The reactor vial was then sealed under nitrogen and placed in a sealedreactor block. After 3 hours at 90° C., the reaction mixture was allowedto cool to room temperature. The reaction mixture was acidified with 15%aqueous HCl, producing a precipitate. The precipitate was filtered andwashed with H₂O and the dried product was analyzed by ¹H NMR. Percentconversion of DBTA (II) for each ligand is presented in Table 2.Selectivities for DHTA (I) and the intermediate2-bromo-5-dihydroxyterephalic acid (VII) are also presented in Table 2.Using either a methyl-bearing tertiary tetraamine (Ligand O, ComparativeExample A) or no ligand (Comparative Example B) resulted in lowerconversion than using the ligands of the working examples.

TABLE 2 I

II

VII

Ligand CONV SEL SEL Ligand Code Example (II, %) (VII, %) (I, %)Structure A  3 >99 <1 84

B  4 >99 <1 94

C  5 92 5% 12

D  6 >99 <1 90

E  7 98 4 12

F  8 >99 <1 >98

G  9 >99 <1 82

H 10 83 9 10

I 11 >99 <1 55

J 12 >99 <1 76

K 13 >99 <1 96

L 14 >99 <1 11

M 15 >99 2 58

N 16 >99 3 49

O A(Comparative) 64 17 11

P 17 >99 <1 99

Q 18 >99 <1 88

R 19 >99 <1 75

— B 31 32 2 No ligand (Comparative) (Comparative)

Examples 20-23

Eight 2 mL reaction vials were each charged with 25 mg (0.077 mmol) of2,5-dibromoterephthalic acid, followed by various amounts of 0.5 Maqueous sodium carbonate solution as shown in Table 3. Each of themixtures was then treated with 0.003 mL of 0.23 M copper(I) bromide inacetonitrile and 0.003 mL of 0.5 Mrac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F). The reactionvials were closed and loaded into an 8-well reactor. The reactor wasthen sealed. About 12 psi (83 kPa) of N₂ pressure was applied. Thereactor was heated to 90° C. and held at that temperature for 5 hours,then allowed to cool to room temperature. The reaction mixture was thenacidified with 15% aqueous HCl, producing a light green precipitate. Theprecipitate was filtered, washed with water, dried, and analyzed by ¹HNMR in DMSO-d6. Results are presented in Table 3.

TABLE 3 Amount Na₂CO₃ [in equivalents % yield * by Example of Na⁺] ¹HNMR 20 4.1 97 21 4.2 99 22 4.5 99 23 5 99 * Average of two values

Examples 24-29

These examples demonstrate the formation of 2,5-dihydroxyterephthalicacid from 2,5-dibromoterephthalic acid using different copper compoundsand rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F). Undernitrogen, a predetermined amount of 2,5-dibromoterephthalic acid (setforth in Table 4) was combined with about the five times the weight H₂O,and a predetermined amount of Na₂CO₃ (set forth in Table 4) was thenadded. The mixture was heated to reflux with stirring for 30 min,remaining under a nitrogen atmosphere. Separately a predetermined amountof the copper compound (set forth in Table 4) and ofrac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F) were combinedwith 2 mL H₂O under exclusion of air. For CuBr and CuCl the resultingmixture was subsequently stirred under an air atmosphere for about 30seconds until the copper salt was dissolved before it was added to thereaction mixture. For CuBr₂, CuSO₄, Cu(OTf) (Toluene) and Cu(OTf)₂, theresulting catalyst solutions were added to the stirred reaction mixturevia syringe at 80° C. under exclusion of air and stirred at 80° C.Samples were taken periodically to follow the conversion to DHTA. Table4 gives the results as derived by ¹H NMR spectroscopy. Times givenindicate the approximate reaction time to reach the given conversion ofstarting material II.

TABLE 4 Cu Ligand DBTA Na₂CO₃ Cu amount amount amount amount Time SELCONV Example source (mmol) (mmol) (mmol) (mmol) Air [h] [%] [%] 24 CuBr0.02 0.04 2 5 Yes ~1 >99 >99 25 CuBr₂ 0.02 0.04 2 5 No ~1 >99 >99 26CuOTf 0.005 0.01 0.5 1.25 No 2.5 98 99 27 Cu(OTf)₂ 0.02 0.04 2 5 No~1 >99 >99 28 CuCl 0.02 0.04 2 5 Yes 8.5 98 99 29 CuSO₄ 0.02 0.04 2 5 No~1 >99 >99

Example 30

This example demonstrates the formation of 2,5-dihydroxyterephthalicacid from 2,5-dichloroterephthalic acid using CuBr andrac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F). Undernitrogen, 2.00 g (8.51 mmol) of 2,5-dichloroterephthalic acid wascombined with 10 g of H₂O. 0.938 g (8.85 mmol) of Na₂CO₃ was then added.The mixture was heated to reflux with stirring for 30 min, remainingunder a nitrogen atmosphere. Another 1.31 g (12.34 mmol) of Na₂CO₃ wasadded to the reaction mixture and reflux was continued for 30 min.Separately, 12 mg of CuBr and 24 mg ofrac-trans-N,N′-dimethylcyclohexane-1,2-diamine (Ligand F) were combinedwith 2 mL H₂O under nitrogen. The resulting mixture was stirred under anair atmosphere until the CuBr was dissolved to give a deep purplesolution. This solution was added to the stirred reaction mixture viasyringe at 80° C. under nitrogen and stirred for 20 h at 80° C. Aftercooling to 25° C., the reaction mixture was acidified with HCl (conc.),producing a dark yellow precipitate. The yellow precipitate was filteredand washed with water. After drying, a total of 1.59 g (8.03 mmol, 94%yield) 2,5-dihydroxyterephthalic acid was collected. The purity wasdetermined by ¹H NMR to be >95%.

Where an embodiment of this invention is stated or described ascomprising, including, containing, having, being composed of or beingconstituted by certain features, it is to be understood, unless thestatement or description explicitly provides to the contrary, that oneor more features in addition to those explicitly stated or described maybe present in the embodiment. An alternative embodiment of thisinvention, however, may be stated or described as consisting essentiallyof certain features, in which embodiment features that would materiallyalter the principle of operation or the distinguishing characteristicsof the embodiment are not present therein. A further alternativeembodiment of this invention may be stated or described as consisting ofcertain features, in which embodiment, or in insubstantial variationsthereof, only the features specifically stated or described are present.

Where the indefinite article “a” or “an” is used with respect to astatement or description of the presence of a step in a process of thisinvention, it is to be understood, unless the statement or descriptionexplicitly provides to the contrary, that the use of such indefinitearticle does not limit the presence of the step in the process to one innumber.

Where a range of numerical values is recited herein, unless otherwisestated, the range is intended to include the endpoints thereof, and allintegers and fractions within the range. It is not intended that thescope of the invention be limited to the specific values recited whendefining a range.

1-17. (canceled)
 18. A process for preparing a 2,5-dialkoxyterephthalicacid comprising the step of: (a) contacting a 2,5-dihaloterephthalicacid, as described generally by Formula III

wherein X=Cl, Br, or I, with base in water to form therefrom thecorresponding dibasic salt of the 2,5-dihaloterephthalic acid; (b)contacting the dibasic salt of the 2,5-dihaloterephthalic acid with basein water, and with a copper source in the presence of an amine ligandthat coordinates to copper, to form the dibasic salt of2,5-dihydroxyterephthalic acid from the dibasic salt of2,5-dihaloterephthalic acid at a solution pH of at least about 8;wherein the ligand comprises, when it is a tetraamine, at least oneprimary or secondary amino group; (c) optionally, separating the dibasicsalt of 2,5-dihydroxyterephthalic acid from the reaction mixture inwhich it is formed; (d) contacting the dibasic salt of2,5-dihydroxyterephthalic acid with acid to form therefrom2,5-dihydroxyterephthalic acid; and (e) converting the2,5-dihydroxyterephthalic acid to a 2,5-dialkoxyterephthalic acid.
 19. Aprocess according to claim 18 wherein the 2,5-dihydroxyterephthalic acidis contacted under basic conditions with a dialkyl sulfate of theformula R⁹ R¹⁰ SO₄ wherein R⁹ and R¹⁰ are each independently asubstituted or unsubstituted C₁₋₁₀ alkyl group.
 20. A process forpreparing a compound, monomer, oligomer or polymer from a2,5-dihydroxyterephthalic acid comprising the steps of: (a) contractinga 2,5-dihaloterephthalic acid, as described generally by Formula III

wherein X=Cl, Br, or I, with base in water to form therefrom thecorresponding dibasic salt of the 2,5-dihaloterephthalic acid; (b)contacting the dibasic salt of the 2,5-dihaloterephthalic acid with basein water, and with a copper source in the presence of an amine ligandthat coordinates to copper, to form the dibasic salt of2,5-dihydroxyterephthalic acid from the dibasic salt of2,5-dihaloterephthalic acid at a solution pH of at least about 8;wherein the ligand comprises, when it is a tetraamine, at least oneprimary or secondary amino group; (c) optionally, separating the dibasicsalt of 2,5-dihydroxyterephthalic acid from the reaction mixture inwhich it is formed; (d) contacting the dibasic salt of2,5-dihydroxyterephthalic acid with acid to forom therefrom2,5-dihydroxyterephthalic acid; and (e) subjecting the2,5-dihydroxyterephthalic acid to a reaction to prepare therefrom acompound, monomer, oligomer or polymer.
 21. A process according to claim20 wherein a polymer prepared comprises apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer.
 22. Aprocess according to claim 18 further comprising a step of subjectingthe 2,5-dialkoxyterephthalic acid to a reaction to prepare therefrom acompound, monomer, oligomer or polymer.